Investigating the role of evolutionary conserved KRAB-ZFPs

Transposable elements (TEs) of various forms and age constitute ~50% of the human genome. Given their abundance, there is less research into TE function than we would expect - this is mostly due to the widespread perception that they are mostly 'junk DNA' with no appreciable function. As such, it remains poorly understood how this half of our genome contributes to our biology.

KRAB-ZFPs are the largest family of DNA binding factors in tetrapods, displaying enriched binding to TEs. They are transcriptional repressors, and many are evolutionary conserved with TE-targets that are largely degraded. However, the biological functions of many individual members of this protein family are unknown. It is thought that some of the TEs bound by KRAB-ZFPs might have been co-opted as regulatory platforms, perhaps acting as enhancers or alternative promoters.

By focusing on a few KRAB-ZFPs that are conserved between humans and mouse, the aim of this PhD project is to further characterise the roles of conserved KRAB-ZFPs in the domestication of TEs for the regulation of host gene expression. In addition to better defining the biological functions of a few individual KRAB-ZFPs, we aim to reveal some general principles of how the repeat genome is functionally integrated into host genomes, and gain insight into the co-evolutionary relationship between TEs and KRAB-ZFPs.